The long range objective of our research is to elucidate the complex regulatory mechanisms involved in protein homeostasis in normal man. Several hormones (i.e. insulin, glucagon, cortisol, catecholamines and thyroid hormones) and the overall nutritional status can directly or indirectly exert their effects on peripheral tissues and the liver in the th modulation of these processes. Our laboratory has been extensively involved over the past few years in assessing these regulatory effects on the liver in normal man; we are presently planning to extend these studies to the peripheral tissues. To meaningfully assess the direct effects and the complex interaction of these hormones in regulating muscle homeostasis in man, it is necessary to measure 1) peripheral substrate release, 2) total body amino acid kinetics and 3) the efficiency of transamination and oxidation of these amino acids. To accomplish this, we utilize a heated superficial hand vein (a suitable substitute for the arter), and a depp forearm vein, combined with he constant infusion of L-1-14C-leucine and the measurement of forearm blood flow. Utilizing these techniques we wish to accomplish the following: (1) to determine in normal man the metabolic changes that occur with early starvation (12h, 36h and 60h) with special reference to the kinetics of leucine and its keto-acid, Alpha-keto-isocarproate, and to forearm metabolism during those periods; (2) to evaluate the influence of residual insulin secretion on in situ metabolism by (a) producing insulinopenia via infusion of somatostatin and (b) by replacing basal insulin levels during somatostatin infusion. Finally we will, (3) evaluate the influence of hypercortisolism of differing duration perse and its interaction with progressive stages of fasting on all these metabolic processes. These studies will provide considerable insight into the mechanisms of enhanced amino acid fluxes and protein breakdown in such disease states as trauma, sepsis, infection, diabetes mellitus etc.., information which may ultimately be translated into improved health care for such patients.